[KSCI] Korea Science Citation Index Service

http://dx.doi.org/10.5483/BMBRep.2017.50.7.063

Repression of the F-box protein Skp2 is essential for actin damage-induced tetraploid G1 arrest

Jo, Yongsam (Department of Microbiology, Dankook University College of Medicine)
Shin, Deug Y. (Department of Microbiology, Dankook University College of Medicine)

Publication Information

BMB Reports / v.50, no.7, 2017 , pp. 379-383 More about this Journal

Abstract

We previously reported that p53 plays a role as a key regulator in the tetraploid G1 checkpoint, which is activated by actin damage-induced cytokinesis blockade and then prevents uncoupled DNA replication and nuclear division without cytokinesis. In this study, we investigated a role of Skp2, which targets CDK2 inhibitor p27/Kip1, in actin damage-induced tetraploid G1 arrest. Expression of Skp2 was reduced, but p27/Kip1 was increased, after actin damage-induced cytokinesis blockade. The role of Skp2 repression in tetraploid G1 arrest was investigated by analyzing the effects of ectopic expression of Skp2. After actin damage, ectopic expression of Skp2 resulted in DNA synthesis and accumulation of multinucleated cells, and ultimately, induction of apoptosis. These results suggest that Skp2 repression is important for sustaining tetraploid G1 arrest after cytokinesis blockade and is required to prevent uncoupled DNA replication and nuclear division without cytokinesis.

Keywords

Actin damage; Cytokinesis; Pectenotoxin-2; Skp2; Tetraploid G1 arrest;

Citations & Related Records

Reference

1	Hartwell LH and Weinert TA (1989) Checkpoints: controls that ensure the order of cell cycle events. Science 246, 629-634 DOI
2	Kuerbitz SJ, Plunkett BS, Walsh WV and Kastan MB (1992) Wild-type p53 is a cell cycle checkpoint determinant following irradiation. Proc Natl Acad Sci U S A 89, 7491-7495 DOI
3	Bunz F, Dutriaux A, Lengauer C et al (1998) Requirement for p53 and p21 to sustain G2 arrest after DNA damage. Science 282, 1497-1501 DOI
4	Lanni JS and Jacks T (1998) Characterization of the p53-dependent postmitotic checkpoint following spindle disruption. Mol Cell Biol 18, 1055-1064 DOI
5	Khan S and Wahl G (1998) p53 and pRb prevent rereplication in response to microtubule inhibitors by mediating a reversible G1 arrest. Cancer Res 58, 396-401
6	Di Leonardo A, Khan S, Linke S, Greco V, Seidita G and Wahl G (1997) DNA rereplication in the presence of mitotic spindle inhibitors in human and mouse fibroblasts lacking either p53 or pRb function. Cancer Res 57, 1013-1019
7	Andreassen PR, Lohez OD, Lacroix FB and Margolis RL (2001) Tetraploid state induces p53-dependent arrest of nontransformed mammalian cells in G1. Mol Biol Cell 12, 1315-1328 DOI
8	Chae HD, Choi TS, Kim BM, Jung JH, Bang YJ and Shin DY (2005) Oocyte-based screening of cytokinesis inhibitors and identification of pectenotoxin-2 that induces Bim/Bax-mediated apoptosis in p53-deficient tumors. Oncogene 24, 4813-4819 DOI
9	Yun UJ, Park HD and Shin DY (2006) p53 prevents immature escaping from cell cycle G2 checkpoint arrest through inhibiting cdk2-dependent NF-Y phosphorylation. Cancer Res Treat 38, 224-228 DOI
10	Cheng M, Olivier P, Diehl JA et al (1999) The p21(Cip1) and p27(Kip1) CDK 'inhibitors' are essential activators of cyclin D-dependent kinases in murine fibroblasts. EMBO J 18, 1571-1583 DOI
11	Carrano AC, Eytan E, Hershko A, Pagano M (1999) SKP2 is required for ubiquitin-mediated degradation of the CDK inhibitor p27. Nat Cell Biol 1, 193-199 DOI
12	Frescas D and Pagano M (2008) Deregulated proteolysis by the F-box proteins SKP2 and beta-TrCP: tipping the scales of cancer. Nat Rev Cancer 8, 438-449 DOI
13	Chae HD, Kim SY, Park SE, Kim J and Shin DY (2012) p53 and DNA-dependent protein kinase catalytic subunit independently function in regulating actin damage-induced tetraploid G1 arrest. Exp Mol Med 44, 236-240 DOI
14	Traub F, Mengel M, Luck HJ, Kreipe HH and von Wasielewski R (2006) Prognostic impact of Skp2 and p27 in human breast cancer. Breast Cancer Res Treat 99, 185-191 DOI
15	Sutterluty H, Chatelain E, Marti A et al (1999) p45SKP2 promotes p27Kip1 degradation and induces S phase in quiescent cells. Nat Cell Biol 1, 207-214 DOI
16	Lin HK, Chen Z, Wang G et al (2010) Skp2 targeting suppresses tumorigenesis by Arf-p53-independent cellular senescence. Nature 464, 374-379 DOI
17	Chae H, Kim B, Yun U and Shin D (2008) Deregulation of Cdk2 causes Bim-mediated apoptosis in p53-deficient tumors following actin damage. Oncogene 27, 4115-4121 DOI
18	Chae HD, Choi TS, Kim BM, Jung JH, Bang YJ and Shin DY (2005) Oocyte-based screening of cytokinesis inhibitors and identification of pectenotoxin-2 that induces Bim/Baxmediated apoptosis in p53-deficient tumors. Oncogene 24, 4813-4819 DOI
19	Amati B and Vlach J (1999) Kip1 meets SKP2: new links in cell-cycle control. Nat Cell Biol 1, E91-93 DOI
20	Wei W, Ayad NG, Wan Y, Zhang GJ, Kirschner MW and Kaelin WG Jr (2004) Degradation of the SCF component Skp2 in cell-cycle phase G1 by the anaphase-promoting complex. Nature 428, 194-198 DOI
21	Ganiatsas S, Dow R, Thompson A, Schulman B and Germain D (2001) A splice variant of Skp2 is retained in the cytoplasm and fails to direct cyclin D1 ubiquitination in the uterine cancer cell line SK-UT. Oncogene 20, 3641-3650 DOI
22	Park M, Chae HD, Yun J et al (2000) Constitutive activation of cyclin B1-associated cdc2 kinase overrides p53-mediated G2-M arrest. Cancer Res 60, 542-545
23	Chae HD, Yun J, Bang YJ and Shin DY (2004) Cdk2-dependent phosphorylation of the NF-Y transcription factor is essential for the expression of the cell cycleregulatory genes and cell cycle G1/S and G2/M transitions. Oncogene 23, 4084-4088 DOI
24	Jung MS, Jin DH, Chae HD et al (2004) Bcl-xL and E1B-19K proteins inhibit p53-induced irreversible growth arrest and senescence by preventing reactive oxygen species-dependent p38 activation. J Biol Chem 279, 17765-17771 DOI

Reference

12	(2017) International Journal of Molecular Sciences Volasertib Enhances Sensitivity to TRAIL in Renal Carcinoma Caki Cells through Downregulation of c-FLIP Expression / 18 (12) , 2568
1	(2017) Drug Development Research Angelicin potentiates TRAIL-induced apoptosis in renal carcinoma Caki cells through activation of caspase 3 and down-regulation of c-FLIP expression / 79 (1) , 3
11	(2018) Molecules Maritoclax Enhances TRAIL-Induced Apoptosis via CHOP-Mediated Upregulation of DR5 and miR-708-Mediated Downregulation of cFLIP / 23 (11) , 3030
7	(2018) Molecules Garcinol Enhances TRAIL-Induced Apoptotic Cell Death through Up-Regulation of DR5 and Down-Regulation of c-FLIP Expression / 23 (7) , 1614
9	(2018) Molecules Involvement of Up-Regulation of DR5 Expression and Down-Regulation of c-FLIP in Niclosamide-Mediated TRAIL Sensitization in Human Renal Carcinoma Caki Cells / 23 (9) , 2264
11	(2018) Molecules HSP70 Acetylation Prevents Combined mTORC1/2 Inhibitor and Curcumin Treatment-Induced Apoptosis / 23 (11) , 2755
10	(2018) International Journal of Molecular Sciences Cepharanthine Enhances TRAIL-Mediated Apoptosis Through STAMBPL1-Mediated Downregulation of Survivin Expression in Renal Carcinoma Cells / 19 (10) , 3280
38	(2018) Oncogene mTORC1/2 inhibitor and curcumin induce apoptosis through lysosomal membrane permeabilization-mediated autophagy / 37 (38) , 5205
8	(2018) Experimental & Molecular Medicine Z-FL-COCHO, a cathepsin S inhibitor, enhances oxaliplatin-mediated apoptosis through the induction of endoplasmic reticulum stress / 50 (8)